Previous research has demonstrated that, at equivalent blood alcohol levels, children of alcoholics show different effects of ethanol on a variety of outcome measures as compared with family history negative subjects. In a series of controlled experiments in an outpatient research setting, the present project will examine the pharmacological specificity of these differential responses to ethanol by characterizing dose-effect responses to two other drug classes in FHP versus FHN subjects. Additionally, the basic pharmacological process of acute tolerance will be examined across drug classes since this process may contribute to decreased ethanol sensitivity reported for FHP subjects. To facilitate data comparison across studies, a comprehensive battery of physiological, psychomotor and subjective measures will be used throughout the project. Experiment 1 will examine differences in baseline responding, provide partial replication of earlier studies examing acute effects of ethanol administration, and assess acute tolerance development to ethanol in FHP and FHN subjects. Experiments 2A and 3A will examine the pharmacological specificity of the differential ethanol response by characterizing dose-effect relationships of two other drug classes in FHP and FHN subjects: 1) the barbiturate secobarbital, which shows cross-tolerance to ethanol (Exp. 2A); and 2) the opioid analgesic hydromorphone, since recent research has shown possible involvement of the endogenous opiod system in alcohol's actions (Exp. 3A). Experiment 2B, using comparable procedures to those in Experiment 1, will examine acute tolerance development for secobarbital in FHP and FHN subjects. Finally, Experiment 3B will use the naloxone challenge procedure to examine possible differences in acute opiate sensitivity in FHP and FHN subjects; recent studies have found naloxone-precipitated withdrawal symptoms following a single administration of an opiate drug. This series of studies will further the basic understanding of the pharmacology of ethanol effects in FHP versus FHN persons and the generality of differential sensitivity across drug classes.